tbuckley/cabot-search huggingface dataset:
P01.01.A Lesion-Function Analysis from Multimodal Imaging and Normative Brain Atlases for Prediction of Cognitive Deficits in Glioma Patients
Authors: M Kocher, C Jockwitz, P Lohmann, G Stoffels, C Filss, F M Motthagy, M I Ruge, C Weiss Lucas, R Goldbrunner, N J Shah, G R Fink, N Galldiks, K Langen, S Caspers
Journal: Neuro-Oncology (2022)

Abstract Background Cognitive deficits are common in glioma patients following multimodality therapy, but the relative impact of different types and locations of treatment-related brain damage and recurrent tumors on cognition is not well understood. Material and Methods In 121 WHO Grade III/IV glioma patients, structural MRI, O-(2-[18F]fluoroethyl)-L-tyrosine FET-PET, and neuropsychological testing were performed at a median interval of 14 months (range, 1-214 months) after therapy initiation. Resection cavities, T1-enhancing lesions, T2/FLAIR hyperintensities, and FET-PET positive tumor sites were semiautomatically segmented and elastically registered to a normative, resting state (RS) fMRI-based functional cortical network atlas and to the JHU atlas of white matter (WM) tracts, and their influence on cognitive test scores relative to a cohort of matched healthy subjects was assessed. Results T2/FLAIR hyperintensities presumably caused by radiation therapy covered more extensive brain areas than the other lesion types and significantly impaired cognitive performance in many domains when affecting left-hemispheric RS-nodes and WM-tracts as opposed to brain tissue damage caused by resection or recurrent tumors. Verbal episodic memory proved to be especially vulnerable to T2/FLAIR abnormalities affecting the nodes and tracts of the left temporal lobe. Conclusion In order to improve radiotherapy planning, publicly available brain atlases, in conjunction with elastic registration techniques, should be used, similar to neuronavigation in neurosurgery.
OS09.7.A Experiences and unmet needs of grade 2-4 glioma patients and (health care) professionals regarding (return to) work: the BrainWork study
Authors: A Zegers, P Coenen, A Heeren, N Takke, H Ardon, A Compter, D Dona, M Kouwenhoven, S Schagen, F de Vos, S Duijts
Journal: Neuro-Oncology (2022)

Abstract Background In the Netherlands, 1,200 persons are annually diagnosed with a glioma, of whom many are of working age. Studies regarding cancer and work often exclude primary brain tumour patients, due to specific problems these patients may experience. Hence, the aim was to explore the experiences and unmet needs regarding return to work, work retention, or work discontinuation of both grade 2-4 glioma patients, and involved (health care) professionals. Material and Methods Individual semi-structured interviews were held with grade 2-4 glioma patients as well as health care and occupational professionals involved in (the care for) glioma patients. Grade 2-4 glioma patients were eligible to participate if they were of working age and had an employment contract at time of diagnosis. Recruitment of patients was performed via three hospitals and via social media. The professionals were recruited via the network of researchers linked to BrainWork. Interviews were transcribed verbatim, and thematically analysed using ATLAS.ti9. Results Nineteen glioma patients participated in this study (68% male, mean age 45 (SD 11), 58% grade 2, 16% grade 3, 26% grade 4). The main themes identified were: 1) impact of glioma-specific consequences on work ability, 2) communicating about an invisible, progressive illness at work: discrepancies in perceptions, 3) working with a brain tumour: looking at possibilities, and 4) navigating offers of (work-related) support. Sixteen professionals were interviewed (e.g., clinical neuro-oncologist, insurance physician) with an average experience of fifteen years. Four key themes were identified: (1) distilling the right approach: generic or specific vocational rehabilitation?; (2) work adjustments are common, but information deficiency causes delay; (3) opinions about work ability are diverse and influenced by glioma-specific characteristics; and (4) need for attention and tailored recommendations regarding glioma and work. Conclusions Working is possible for glioma patients although they encounter glioma-specific problems, and commonly need work adjustments. These adjustments should be communicated early, to prevent employer-employee conflicts. A specific reintegration plan, including a neuropsychological assessment and a glioma-tailored rehabilitation program, is considered the most adequate approach. Open communication between the patient and the (work) environment in general is necessary to abate discrepancies in perception. Communication between health care professionals and occupational professionals should be improved to diminish differences in opinions about the work ability of glioma patients. Finally, more attention and more tailored recommendations regarding glioma and work are necessary.
P01.02.B Case Report: Disruption of Resting-State Networks and Cognitive Deficits After Whole Brain Irradiation for Singular Brain Metastasis
Authors: M Kocher, C Jockwitz, C Lerche, M Sabel, P Lohmann, G Stoffels, C Filss, F M Motthagy, M I Ruge, G R Fink, N J Shah, N Galldiks, S Caspers, K Langen
Journal: Neuro-Oncology (2022)

Abstract Background Long-term survivors of whole brain radiation (WBRT) are at significant risk for developing cognitive deficits, but knowledge about the underlying pathophysiological mechanisms is limited. Therefore, we here report a rare case with a singular brain metastasis treated by resection and WBRT that survived for more than 10 years where we investigated the integrity of brain networks using resting-state functional MRI. Material and Methods A female patient with a left frontal non-small cell lung cancer (NSCLC) brain metastasis had resection and postoperative WBRT (30.0 in 3.0Gy fractions) and stayed free from brain metastasis recurrence for a follow-up period of 11 years. Structural magnetic resonance imaging (MRI) and amino acid [O-(2-[18F]fluoroethyl)-L-tyrosine] positron emission tomography (FET PET) were repeatedly acquired. At the last follow up, neurocognitive functions and resting-state functional connectivity (RSFC) using resting-state fMRI were assessed. Within-network and inter-network connectivity of seven resting-state networks were computed from a connectivity matrix. All measures were compared to a matched group of 10 female healthy subjects. Results At the 11-year follow-up, T2/FLAIR MR images of the patient showed extended regions of hyper-intensities covering mainly the white matter of the bilateral dorsal frontal and parietal lobes while sparing most of the temporal lobes. Compared to the healthy subjects, the patient performed significantly worse in all cognitive domains that included executive functions, attention and processing speed, while verbal working memory, verbal episodic memory, and visual working memory were left mostly unaffected. The connectivity matrix showed a heavily disturbed pattern with a widely distributed, scattered loss of RSFC. The within-network RSFC revealed a significant loss of connectivity within all seven networks where the dorsal attention and fronto-parietal control networks were affected most severely. The inter-network RSFC was significantly reduced for the visual, somato-motor, and dorsal and ventral attention networks. Conclusion As demonstrated here in a patient with a metastatic NSCLC and long-term survival, WBRT may lead to extended white matter damage and cause severe disruption of the RSFC in multiple resting state networks. In consequence, executive functioning which is assumed to depend on the interaction of several networks may be severely impaired following WBRT apart from the well-recognized deficits in memory function.
P01.21.A Testing Semantic Verbal Fluency (SVFT) in patients with headache suspicious of cancer helps predict those with tumour on imaging
Authors: K Zienius, W Hewins, D Summers, L McKinlay, P Brennan, L Porteous, R Grant
Journal: Neuro-Oncology (2022)

Abstract Background Differentiating secondary headache from primary headache on history alone can sometimes be difficult. Headache “plus” other subtle cognitive features improves prediction. Patients and relatives may attribute subtle cognitive or behavioural changes to other causes (e.g. anxiety, low mood). Sematic verbal fluency - “how many animals can you think of in a minute” is commonly impaired on admission in patients with headache harbouring a tumour. We were interested whether SVFT at point of referral for scan would help predict a tumour and requested GPs report the SVFT on electronic referral for direct access scanning in cases with a history of headache suspicious of cancer. The aim of the pilot study was to establish if the SVFT was a “red flag” for secondary causes of headache. We report the results of a 20-month audit of cases. Material and Methods An electronic Protocol Based Referral (PBR) was developed for Headache Suspicious of Cancer to expedite scanning. The PBR sat alongside the routine e-DACI system that had been in use for some years. The GP was asked to complete the SVFT at the time of referral for scanning. Other data were gathered: PMH cancer; other symptoms/signs; co-morbid conditions and medications. Results GPs submitted requests for ePBR scanning in 669 cases over 20 months (62% females; Mean age 53: 60% &amp;lt;60 years). SVFT was completed on the request form in 381 (57%) cases. In these cases median SVFT was 17 animals. 11/381 cases were found to have cancer on scanning (2.9%): 10/188 cases with intracranial tumours had a SVFT &amp;lt;17 (5.32%) compared with one with a SVFT &amp;gt;=17. The median SVFT in cases with cancer was 10 animals. Other possible causes of SVFT &amp;lt;17 were - 53 psychiatric or chronic pain conditions on multiple drugs;12 were not native English speakers; 19 had co-existing dementia; 5 had small vessel disease; 4 cysts; 4 Giant Cell Arteritis ; 2 Chiari 1 malformation; PMH - encephalitis (1). Conclusion A SVFT result &amp;lt;17, at the point of referral for brain imaging, in patients with headache suspicious of cancer was associated with intracranial cancer in more than 1:20 cases, whereas a SVFT of &amp;gt;=17 was associated with cancer in 1:200 cases. SVFT may be an additional useful “red flag”. The most appropriate SVFT cut-off requires more research in a larger study. Low SVFT in headache patients may inform Cancer Referral Guidelines, improve the identification of secondary headache and help expedite cases.
P06.06.B standardization of therapy and manufacturing using tumor-associated antigen-stimulated autologous dendritic cells co-cultured with cytokine-induced killer cells in cancer immunotherapy
Authors: C M Yen, Y Y Fu, M Y Yang
Journal: Neuro-Oncology (2022)

Abstract Background The application of DC-CIK in the field of cancer immunotherapy has been shown to be an effective treatment. However, the cost of DC-CIK treatment is prohibitive for many patients, and the lack of standard manufacturing processes and treatment strategies are the main limitations. Material and Methods Our experiments used tumor lysate instead of tumor cell line as tumor-associated antigen source with DCs co-culture. We provide the most efficient method for obtaining autologous DC-CIK cells from peripheral blood. Flow cytometry was used to evaluate DCs activation, CBA assay was used to quantify cytokines secreted by CIK cells, and the antitumor activity of DC-CIK was evaluated in vitro by K562 cell line. Results We demonstrate that the manufacturing process of employing frozen Peripheral Blood Mononuclear Cells (PBMCs) can balance patient’s comfort and economic benefits. DC-CIK can effectively upgrade the immunological specificity of CIK cells to tumors in the presence of tumor-associated antigen. In vitro experiments showed that when the number of DC: CIK cells was co-cultured in 1:20 ratio on the 14th day, the amount of cytokine secreted by CIK cells was the largest, and the anti-tumor immune effect was the most potent. When the number of CIK: K562 cells was in 25:1 ratio, the cytotoxic activity of CIK on K562 cells was the highest. Conclusion We developed an efficient activated fashion of DC:CIK, established the optimal ratio of DC-CIK immunologic activity and the best cytotoxic model of CIK to K562 cells.
P03.02.B Vestibular side effects following robotic guided stereotactic radiosurgery of vestibular schwannoma
Authors: D Rueß, L Pöhlmann, S Jünger, M Kocher, M Ruge
Journal: Neuro-Oncology (2022)

Abstract Background New-onset vestibular disorders (VD), such as dizziness and imbalance, are common side effects after stereotactic radiosurgery (SRS) for vestibular schwannomas (VS). Although these symptoms can severely affect the daily life of VS patients, there are limited data available providing prognostic information on the risk of developing VD after SRS. Material and Methods We included patients who received Cyberknife® SRS for newly diagnosed unilateral VS between 2012 and 2015. The incidence of vestibular disorders before and after treatment was recorded and correlated with tumor, patient, and treatment characteristics. Results We identified 71 patients with a median age of 58 years (range: 21-82) and a median follow-up of 66 months (range: 3-105). Tumor volume before treatment was 1.5 cm3 ± 1.4 (range: 0.1-8.6). A mean marginal dose of 12.9 Gy ± 0.3 (range: 12-14) was administered, and all studied patients remained free of tumor recurrence. Forty-one (58%) of the patients had VD prior to SRS. Of the remaining 30 patients who did not have VD before treatment, 16 (53%) developed new VD (vertigo, n=4; balance disorders, n=8; mixture of VD, n=4). The median time to onset of symptoms was 6 months (range: 2-36). In most patients (n=11, 69%), the new symptoms completely resolved within a median time of 21 months (range: 1-63). In multivariate analysis, neither tumor volume (p=0.7), age (p=0.06), nor radiation dose (p=0.16) were significantly associated with the occurrence of VD. Conclusion In this cohort, about half of the patients develop new onset of transient VD after SRS. The incidence of VD after SRS was found to be independent from usual tumor-, patient- and treatment-related factors. Therefore, a detailed analysis of the dose exposure to the structures of the vestibular apparatus is recommended.
P08.02.B The Clinical Frailty Scale as predictor of overall survival after resection of high-grade glioma
Authors: J Klingenschmid, A Krigers, D Pinggera, J Kerschbaumer, C Thomé, C F Freyschlag
Journal: Neuro-Oncology (2022)

Abstract Background The Clinical Frailty Scale (CFS) describes the general level of fitness or frailty and is widely used in geriatric medicine, intensive care and orthopaedic surgery. This study was conducted to analyze, whether CFS could be used for patients with high-grade glioma. Material and Methods Patients harboring high-grade gliomas, undergoing first resection at our center between 2015 and 2020 were retrospectively evaluated. Patients’ performance was assessed using the Rockwood Clinical Frailty Scale and the Karnofsky Performance Scale (KPS) preoperatively and 3-6 months postoperatively. Results 289 patients were included. Pre- as well as postoperative median frailty was 3 CFS points (IqR 2-4) corresponding to “managing well”. CFS strongly correlated with KPS preoperatively (r = -0.85; p &amp;lt; 0.001) and at the 3-6 months follow-up (r = -0.90; p &amp;lt; 0.001). The reduction of overall survival (OS) was 54% per point of CFS preoperatively (HR 1.54, CI95% 1.38-1.70; p &amp;lt; 0.001) and 58% at the follow-up (HR 1.58, CI95% 1.41-1.78; p &amp;lt; 0.001), comparable to KPS. Patients with IDH mutation showed significantly better preoperative and follow-up CFS and KPS (p &amp;lt; 0.05). Age and performance scores correlated only mildly with each other (r = 0.21⋯0.35; p &amp;lt; 0.01), but independently predicted OS (p &amp;lt; 0.001 each). Conclusion CFS seems to be a reliable tool for functional assessment of patients suffering from high-grade glioma. CFS includes non-cancer related aspects and therefore is a contemporary approach for patient evaluation. Its projection of survival can be equally estimated before and after surgery. IDH-mutation caused longer survival and higher functionality.
P08.03.A Conversation tool for brain tumor patients - tailor-made support and guidance for the patient and their proxies
Authors: K Dujardin, R de Peuter, L Dirven, A Gijtenbeek, E Manten-Horst, M Baas-Thijssen
Journal: Neuro-Oncology (2022)

Abstract Background An evaluation by the Dutch Neuro-Oncology Society (LWNO) showed that screening for psychosocial problems and the need for psychosocial care in glioma patients and their proxies is currently not optimal. Although tools to screen for psychosocial issues such as the Distress Thermometer exist, in daily practice they appear to be insufficient to discuss all disease-specific problems patients with brain tumors may encounter. We describe the development of a conversation tool to support the consultation between the patient with a brain tumor, their proxies and the health care professionals (HCPs). Material and Methods The development of the conversation tool for brain tumors was based on the tool used by the AYA Care Network in the Netherlands. Topics of importance for the entire care process were identified in a brainstorming session with 15 people (comprising HCPs, patients and proxies). Subsequently, the content of the conversation tool was determined by members of the LWNO and members of the LWNO-working group of nurses specialized in neuro-oncology (LWNO-v). Each topic in the conversation tool is supported by a visual, which was developed by a graphic design company in close collaboration with patients, proxies and HCPs. Results The conversation tool contains a total of 35 different topics covering six domains: physical health, daily life activities, psychological health, social relationships, loss of health and life, practical issues, all illustrated by a visual. The conversation tool can be given to the patient in booklet form before an appointment with the HCP, so they can prepare the conversation upfront. In addition, cards per domain will be available in the consultation room to be used during the appointment. Conclusion: By using the conversation tool, optimal individual guidance and support of patients with brain tumors is facilitated, as this patient population has unique issues that are often not covered by exiting tools. Using the conversation tool also promotes a nationally uniform way of working. Currently, an interactive tool for HCPs is being developed in which an overview of available interventions and best practices for the topics in the conversation tool are described, to ensure the needs of patients can be adequately addressed. The process of development of this tool can serve as an example for other cancer types.
OS08.5.A Adenovirus-mediated delivery of the MHC-II Transactivator CIITA gene induces tumor cell killing in immunocompetent glioblastoma organoids
Authors: I Salvato, E Klein, G Forlani, A Poli, A Oudin, V Baus, A Golebiewska, R Accolla, S P Niclou, A Marchini
Journal: Neuro-Oncology (2022)

Abstract Background Although immunotherapies represent an encouraging approach against cancer, to date none translated to the clinical benefit in Glioblastoma (GBM). One aspect contributing to this failure is the highly immunosuppressive GBM microenvironment. Our approach to overcome immunosuppression is to increase anti-tumor immune responses via adenovirus (AdV)-mediated delivery of the MHC-II Transactivator (CIITA) gene. CIITA-induced MHC-II expression is anticipated to convert GBM cells into surrogate antigen presenting cells able to prime T helper cells, therefore promoting CD4+ and CD8+ mediated immunity. Material and Methods We generated AdVs containing wild type CIITA (Ad-CIITA) using a replication-defective serotype5 adenoviral backbone. AdVs containing a mutated, non-functional version of CIITA (Ad-CIITA mutant) and an empty CMV promoter (Ad-null) were used as controls. AdV-mediated MHC-II expression was monitored at mRNA, protein and cell surface level. For the functional assessment of anti-tumor immune responses, we developed an advanced human GBM organoid model system consisting of tumor organoids co-cultured with either human peripheral blood mononuclear cells (PBMCs) or isolated CD3+ T cells. T cell mediated tumor cell killing was monitored over time via live cell imaging and flow cytometry. Results We successfully constructed and produced a CIITA-armed AdV that induces MHC-II expression in infected GBM cells, indicating the efficient expression of transcriptionally active CIITA for at least six days post infection. In immunocompetent human GBM organoids, Ad-CIITA infection of tumor cells led to prominent organoid disruption and tumor cell death, an effect that was not observed in the absence of PBMCs or CD3+ T cells. Tumor organoids infected with Ad-CIITA mutant remained intact, demonstrating the implication of cell surface MHC-II molecules in the observed phenotype. Conclusion Our results demonstrate that AdV-mediated delivery of CIITA is a promising strategy to increase T cell mediated immunity against glioblastoma.
P02.02.A Next-generation sequencing (NGS) for identifying actionable molecular alterations in newly diagnosed and recurrent IDHwt-glioblastoma (GBM) patients: a large mono institutional experience
Authors: M Padovan, M Maccari, A Bosio, S Vizzaccaro, I Cestonaro, M Corrà, M Caccese, G Cerretti, M Fassan, V Zagonel, G Lombardi
Journal: Neuro-Oncology (2022)

Abstract Background NGS panels allow the identification of alterations within hundreds of cancer-related genes and can guide a personalized strategy in glioma treatment. Material and Methods From Nov 2019 to Jan 2022 at Veneto Institute of Oncology, Padua, Italy, a large cohort of IDHwt-GBM tissues was analyzed by NGS (FoundationOne®CDx). We identified all potential actionable molecular alterations at diagnosis and/or at recurrence. High tumor mutational burden (TMB) was defined as ≥10 mutations/megabase. Results We analyzed 429 IDHwt-GBM samples: NGS profile was available for 419 samples (97.7%); sample failures in 10 cases (2.3%). 351 (84%) and 68 (16%) GBM samples derived from surgery at diagnosis and recurrence, respectively. All patients received radiotherapy and/or temozolomide as first line therapy. Among all the analyzed samples, the most frequent actionable molecular alterations were: CDKN2A (57%), CDKN2B (53%), EGFR amplification (39%), EGFR mutation (24%), PTEN loss (27%), RB1 (23%), NF1 (18%), PIK3CA (18%), CDK4 (15%), MDM2 (10%), PDGFRA (8%), BRCA1-2 (7%), FGFR1-3 (7%), Myc (6%), JAK (6%), ROS1 (5%), METmut (2%), METampl (2%), BRAF V600E (2%). No NTRK1/2/3 druggable alterations were observed. High TMB was found in 18 samples. The incidence of alteration of EGFR (ampl/mut), RB1, PIK3CA was statistically different between the two subgroups of samples (Fisher test). To date, 10% of patients received a personalized treatment as compassionate use, off-label use or in clinical trials (9 Dabrafenib/Trametinib, 8 Alpelisib, 3 Erdafitinib, 2 Ipatasertib, 1 Alectinib, 1 Capmatinib, 1 Palbociclib, 1 Entrectinib, 1 Pamiparib). Activity analysis is still ongoing. Conclusion NGS is feasible in GBM samples. Potentially, a high rate of patients could receive a personalized treatment. The activity analysis is ongoing. However, the incidence of actionable molecular alterations may differ between diagnosis and recurrent GBM samples.